6rqu: Difference between revisions
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==X-ray crystal structure of H/D exchanged (H/D) small monoclinic unit cell CA IX SV.== | |||
<StructureSection load='6rqu' size='340' side='right'caption='[[6rqu]], [[Resolution|resolution]] 1.39Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6rqu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RQU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RQU FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carbonate_dehydratase Carbonate dehydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.1 4.2.1.1] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6rqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rqu OCA], [http://pdbe.org/6rqu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rqu RCSB], [http://www.ebi.ac.uk/pdbsum/6rqu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rqu ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/CAH9_HUMAN CAH9_HUMAN]] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.<ref>PMID:18703501</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human carbonic anhydrase IX (CA IX) expression is upregulated in hypoxic solid tumours, promoting cell survival and metastasis. This observation has made CA IX a target for the development of CA isoform-selective inhibitors. To enable structural studies of CA IX-inhibitor complexes using X-ray and neutron crystallography, a CA IX surface variant (CA IXSV; the catalytic domain with six surface amino-acid substitutions) has been developed that can be routinely crystallized. Here, the preparation of protiated (H/H), H/D-exchanged (H/D) and deuterated (D/D) CA IXSV for crystallographic studies and their structural comparison are described. Four CA IXSV X-ray crystal structures are compared: two H/H crystal forms, an H/D crystal form and a D/D crystal form. The overall active-site organization in each version is essentially the same, with only minor positional changes in active-site solvent, which may be owing to deuteration and/or resolution differences. Analysis of the crystal contacts and packing reveals different arrangements of CA IXSV compared with previous reports. To our knowledge, this is the first report comparing three different deuterium-labelled crystal structures of the same protein, marking an important step in validating the active-site structure of CA IXSV for neutron protein crystallography. | |||
Structural comparison of protiated, H/D-exchanged and deuterated human carbonic anhydrase IX.,Koruza K, Lafumat B, Nyblom M, Mahon BP, Knecht W, McKenna R, Fisher SZ Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):895-903. doi:, 10.1107/S2059798319010027. Epub 2019 Aug 22. PMID:31588921<ref>PMID:31588921</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6rqu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Carbonate dehydratase]] | |||
[[Category: Large Structures]] | |||
[[Category: Fisher, Z]] | [[Category: Fisher, Z]] | ||
[[Category: Koruza, K]] | [[Category: Koruza, K]] | ||
[[Category: Ca ix]] | |||
[[Category: Carbonic anhydrase]] | |||
[[Category: Proton transport]] | |||
[[Category: Surface variant]] | |||
Revision as of 09:00, 16 October 2019
X-ray crystal structure of H/D exchanged (H/D) small monoclinic unit cell CA IX SV.X-ray crystal structure of H/D exchanged (H/D) small monoclinic unit cell CA IX SV.
Structural highlights
Function[CAH9_HUMAN] Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.[1] Publication Abstract from PubMedHuman carbonic anhydrase IX (CA IX) expression is upregulated in hypoxic solid tumours, promoting cell survival and metastasis. This observation has made CA IX a target for the development of CA isoform-selective inhibitors. To enable structural studies of CA IX-inhibitor complexes using X-ray and neutron crystallography, a CA IX surface variant (CA IXSV; the catalytic domain with six surface amino-acid substitutions) has been developed that can be routinely crystallized. Here, the preparation of protiated (H/H), H/D-exchanged (H/D) and deuterated (D/D) CA IXSV for crystallographic studies and their structural comparison are described. Four CA IXSV X-ray crystal structures are compared: two H/H crystal forms, an H/D crystal form and a D/D crystal form. The overall active-site organization in each version is essentially the same, with only minor positional changes in active-site solvent, which may be owing to deuteration and/or resolution differences. Analysis of the crystal contacts and packing reveals different arrangements of CA IXSV compared with previous reports. To our knowledge, this is the first report comparing three different deuterium-labelled crystal structures of the same protein, marking an important step in validating the active-site structure of CA IXSV for neutron protein crystallography. Structural comparison of protiated, H/D-exchanged and deuterated human carbonic anhydrase IX.,Koruza K, Lafumat B, Nyblom M, Mahon BP, Knecht W, McKenna R, Fisher SZ Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):895-903. doi:, 10.1107/S2059798319010027. Epub 2019 Aug 22. PMID:31588921[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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